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This case report aims to introduce a patient with severe hypokalemia as one of the rare complications of ondansetron injection. The stroke patient was 56 years old and hospitalized in the emergency department with and purulent sputum. The symptoms and lung computed tomography scan confirmed the diagnosis of aspiration pneumonia. A nasogastric tube was inserted, and food gavage was performed for the patient. The treatment was started with meropenem to manage aspiration pneumonia. The patient could not tolerate the gavage. Consequently, ondansetron was prescribed, but severe hypokalemia of 2.5 mEq/l was developed. The causes of hypokalemia were evaluated. The hematological, biochemical, and liver function tests were done, and the potassium level was measured daily. Afterward, causes of hypokalemia was ruled out and with discontinuation of ondansetron the hypokalemia was resolved. Hypokalemia may be caused by ondansetron. It is required that potassium monitoring be always considered during administrating of this medicine.